Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

O Hughes; AR Bentley; CE Breeze; F Aguet; X Xu; G Nadkarni; Q Sun; BM Lin; T Gilliland; MC Meyer; J Du; LM Raffield; H Kramer; RW Morton; MH Gouveia; EG Atkinson; A Valladares-Salgado; N Wacher-Rodarte; ND Dueker; X Guo; Y Hai; A Adeyemo; LG Best; J Cai; G Chen; M Chong; A Doumatey; J Eales; MO Goodarzi; E Ipp; MR Irvin; M Jiang; AC Jones; C Kooperberg; JE Krieger; EM Lange; MB Lanktree; JP Lash; PA Lotufo; RJF Loos; My VT Ha; J Peralta-Romero; L Qi; LJ Raffel; SS Rich; EJ Rodriquez; E Tarazona-Santos; KD Taylor; JG Umans; J Wen; BA Young

doi:10.1016/j.xgen.2023.100468

Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

O Hughes, AR Bentley, CE Breeze, F Aguet, X Xu, G Nadkarni, Q Sun, BM Lin, T Gilliland, MC Meyer, J Du, LM Raffield, H Kramer, RW Morton, MH Gouveia, EG Atkinson, A Valladares-Salgado, N Wacher-Rodarte, ND Dueker, X GuoY Hai, A Adeyemo, LG Best, J Cai, G Chen, M Chong, A Doumatey, J Eales, MO Goodarzi, E Ipp, MR Irvin, M Jiang, AC Jones, C Kooperberg, JE Krieger, EM Lange, MB Lanktree, JP Lash, PA Lotufo, RJF Loos, My VT Ha, J Peralta-Romero, L Qi, LJ Raffel, SS Rich, EJ Rodriquez, E Tarazona-Santos, KD Taylor, JG Umans, J Wen, BA Young

Research output: Contribution to journal › Article › peer-review

Abstract

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

Original language	English
Article number	100468
Journal	Cell genomics
Volume	4
Issue number	1
Early online date	21 Dec 2023
DOIs	https://doi.org/10.1016/j.xgen.2023.100468
Publication status	Published - 10 Jan 2024

Keywords

admixed populations
chronic kidney disease
eGFR
expression quantitative trait locus
fine-mapping
genome-wide association study
kidney function
multi-ancestry
polygenic scores

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.xgen.2023.100468Licence: CC BY-NC-ND

Cite this

Hughes, O., Bentley, AR., Breeze, CE., Aguet, F., Xu, X., Nadkarni, G., Sun, Q., Lin, BM., Gilliland, T., Meyer, MC., Du, J., Raffield, LM., Kramer, H., Morton, RW., Gouveia, MH., Atkinson, EG., Valladares-Salgado, A., Wacher-Rodarte, N., Dueker, ND., ... Young, BA. (2024). Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas. Cell genomics, 4(1), Article 100468. https://doi.org/10.1016/j.xgen.2023.100468

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title = "Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.",

abstract = "Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.",

keywords = "admixed populations, chronic kidney disease, eGFR, expression quantitative trait locus, fine-mapping, genome-wide association study, kidney function, multi-ancestry, polygenic scores",

author = "O Hughes and AR Bentley and CE Breeze and F Aguet and X Xu and G Nadkarni and Q Sun and BM Lin and T Gilliland and MC Meyer and J Du and LM Raffield and H Kramer and RW Morton and MH Gouveia and EG Atkinson and A Valladares-Salgado and N Wacher-Rodarte and ND Dueker and X Guo and Y Hai and A Adeyemo and LG Best and J Cai and G Chen and M Chong and A Doumatey and J Eales and MO Goodarzi and E Ipp and MR Irvin and M Jiang and AC Jones and C Kooperberg and JE Krieger and EM Lange and MB Lanktree and JP Lash and PA Lotufo and RJF Loos and Ha, {My VT} and J Peralta-Romero and L Qi and LJ Raffel and SS Rich and EJ Rodriquez and E Tarazona-Santos and KD Taylor and JG Umans and J Wen and BA Young",

year = "2024",

month = jan,

day = "10",

doi = "10.1016/j.xgen.2023.100468",

language = "English",

volume = "4",

journal = "Cell genomics",

issn = "2666-979X",

publisher = "Cell Press",

number = "1",

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Hughes, O, Bentley, AR, Breeze, CE, Aguet, F, Xu, X, Nadkarni, G, Sun, Q, Lin, BM, Gilliland, T, Meyer, MC, Du, J, Raffield, LM, Kramer, H, Morton, RW, Gouveia, MH, Atkinson, EG, Valladares-Salgado, A, Wacher-Rodarte, N, Dueker, ND, Guo, X, Hai, Y, Adeyemo, A, Best, LG, Cai, J, Chen, G, Chong, M, Doumatey, A, Eales, J, Goodarzi, MO, Ipp, E, Irvin, MR, Jiang, M, Jones, AC, Kooperberg, C, Krieger, JE, Lange, EM, Lanktree, MB, Lash, JP, Lotufo, PA, Loos, RJF, Ha, MVT, Peralta-Romero, J, Qi, L, Raffel, LJ, Rich, SS, Rodriquez, EJ, Tarazona-Santos, E, Taylor, KD, Umans, JG, Wen, J & Young, BA 2024, 'Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.', Cell genomics, vol. 4, no. 1, 100468. https://doi.org/10.1016/j.xgen.2023.100468

TY - JOUR

T1 - Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

AU - Hughes, O

AU - Bentley, AR

AU - Breeze, CE

AU - Aguet, F

AU - Xu, X

AU - Nadkarni, G

AU - Sun, Q

AU - Lin, BM

AU - Gilliland, T

AU - Meyer, MC

AU - Du, J

AU - Raffield, LM

AU - Kramer, H

AU - Morton, RW

AU - Gouveia, MH

AU - Atkinson, EG

AU - Valladares-Salgado, A

AU - Wacher-Rodarte, N

AU - Dueker, ND

AU - Guo, X

AU - Hai, Y

AU - Adeyemo, A

AU - Best, LG

AU - Cai, J

AU - Chen, G

AU - Chong, M

AU - Doumatey, A

AU - Eales, J

AU - Goodarzi, MO

AU - Ipp, E

AU - Irvin, MR

AU - Jiang, M

AU - Jones, AC

AU - Kooperberg, C

AU - Krieger, JE

AU - Lange, EM

AU - Lanktree, MB

AU - Lash, JP

AU - Lotufo, PA

AU - Loos, RJF

AU - Ha, My VT

AU - Peralta-Romero, J

AU - Qi, L

AU - Raffel, LJ

AU - Rich, SS

AU - Rodriquez, EJ

AU - Tarazona-Santos, E

AU - Taylor, KD

AU - Umans, JG

AU - Wen, J

AU - Young, BA

PY - 2024/1/10

Y1 - 2024/1/10

N2 - Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

AB - Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

KW - admixed populations

KW - chronic kidney disease

KW - eGFR

KW - expression quantitative trait locus

KW - fine-mapping

KW - genome-wide association study

KW - kidney function

KW - multi-ancestry

KW - polygenic scores

UR - https://europepmc.org/articles/PMC10794846

U2 - 10.1016/j.xgen.2023.100468

DO - 10.1016/j.xgen.2023.100468

M3 - Article

C2 - 38190104

SN - 2666-979X

VL - 4

JO - Cell genomics

JF - Cell genomics

IS - 1

M1 - 100468

ER -

Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

NIHR Manchester Biomedical Research Centre

Epigenetic Mechanisms of Blood Pressure Regulation & Human Hypertension - Genome-Wide Methylation Analysis of the Human Kidney.

Cite this

Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

NIHR Manchester Biomedical Research Centre

Epigenetic Mechanisms of Blood Pressure Regulation & Human Hypertension - Genome-Wide Methylation Analysis of the Human Kidney.

Cite this